Oncofertility Ovarian Salvage

This topic of oncofertility was something that, um, which I'll tell you, this is what's interesting. Let me tell you a little background on how we designed the these update courses. So the group of the course directors get together, we look at the papers that came out over the past year in JPS or in other journals, we sort of decide what are some things that are highly controversial, some new ideas, things that we think there's some gaps. Recently, um, Apps of PDC has come on board to join us where they have their method of coming up with their gaps. What is fascinating to me is that this year how many overlaps there were when we completely independently came up with our list. Uh, so umbilical access, complete independence, both of us came up with that. Uh, uh, C spine was one that we both came up with. And and now this is the third one that we both came up with, uh, that we felt was important to talk about and that is oncofertility. And we absolutely have an expert to talk to us about it. Uh, Dr. Julie Rios is uh, our oncofertility expert. She's a OBGYN here in uh, Cincinnati Children's and she's going to talk to us about oncofertility. So I just um, went back to kind of what you guys I think were doing this morning with some cases. So this was an interesting case that we just had in the last month of an 11month old female that had a three-month history of constipation, diarrhea, recent visualization of a vaginal mass. So she underwent um exam under anesthesia, cystoscopy, vaginoscopy and biopsy of the mass, which revealed both urethral and uh urethra and bladder involvement. So looking at the mass, um, both urology and my partner in pediatric gynecology said, we think this is a bladder primary and rabdomyo sarcoma was the final uh, diagnosis. So had a pet scan that was negative for lymph nodes. So the treatment plan is going to be um, this D9803, which is Vin Christine, actinomycin and cyclophosphamide. And so we look at dosing of chemotherapy by how what the equivalent is to cyclophosphamide. So that's what the CED means, cyclophosphamide equivalent dose and it was 30.8 grams per meter squared. Anything over 15 in a pediatric patient puts them at high risk for ovarian failure in the future. She's also going to plan for GU radiation for local control. So our oncologist read her treatment plan and we got a risk assessment of the primary ovarian insufficiency risk is high. She's planning to undergo a laparoscopic lymph node dissection, um, for further uh staging. So what would you offer this patient for fertility preservation? Let's look at this. So it looks like there's your answer. It looks like everyone is saying ovarian tissue cryo preservation. Let's throw up a yes, no. The question is, have you heard of fertility preservation? Yes or no? Yes, you've heard of it? No, you haven't. Yes. So I'm just going to go to the next slide just to kind of go through our uh answers. So she's got two things going on. She's getting chemotherapy which will affect the ovaries, she's also getting pelvic radiation, which will affect her uterus and her ovaries as well. So um ovarian transposition or uphoropexy can preserve ovarian function from radiation damage. Um, but the patient's receiving high dose, highly toxic chemotherapy. Um, also in an 11 month old young patients, we may not actually get enough anatomic different distance if it's a pelvic radiation to really prevent that scatter. So that's always a question to talk to the uh radiation oncologist about and to get the SIM to see what the scatter is going to be to those ovaries if we move them. Um, GNRH agonist therapy was something that we did, I mean, I would say not within the most recent years to try to decrease uh fertility uh or increase fertility preservation during chemotherapy. It really has not demonstrated any clear preservation uh for patients. There is some benefit in older patients with breast cancer potentially. The studies conflict um for that as well. Um, but again, if we don't recommend this as our first line, Asco does not recommend this as first line. Um, and so if they have another option available, that's typically what we go with. Um, so this patient was going to have another surgery, so ovarian tissue cryo preservation, it's experimental. Um, it's followed by future ovarian tissue transplantation. Um, that can allow for about 30% of patients to have fertility in the future. Um, most of the data though is from post pubertal patients. But there have been studies to actually look at the ovarian tissue when we pull it out of the pediatric patients and there's visible visible follicles. So there's lots of research, lots of hope that this will be um something that's useful in our pediatric patients as well. And I just wanted to show a little bit of, you know, what we do. So typically you can take a full ovary, you can also take a partial ovary. Um, the tissue is harvested, the cortex is um then cryo preserved. Um, we typically do it within the same day to try to minimize any loss of eggs just from being out of their vascular supply. And then uh later in the future, it's an aus um ovarian cortical tissue transplant. Most of those go back in what we call orthotopic transplantation where it's put back where the ovary came out. So you can sew it to the other ovary, which is what we see on the bottom, the very bottom picture is the tissue strips are sewn to the contralateral ovary that remains. Um, there's also a newer technique where you can just make a peritoneal pocket near the fallopian tube where you remove the the tissue, put the strips so that the cortex where the ovaries will rupture from, their eggs will rupture from, near the peritoneum and they'll just rupture right through the peritoneum. So there's different techniques and um it shows about 37 to 50% of patients that had a transplant um had a live birth. 30 to 40% of people, so some people had multiple transplants. Um, so 30 to 40% of patients will actually have fertility preservation, but 60 to 90% will have ovarian endocrine function. So it's very successful in that restoration. And that's data based on a meta analysis. So, couple questions. Not every place has their own uh, gynecologist in their hospital. How what could the these uh 900 pediatric surgeons do uh at their hospital if they don't necessarily have gynecologist. So if this is something that the patient, I mean, you have to have the whole process. So even if you have someone that can remove an ovary, you have to have someone that can freeze it because you typically freeze it on site. Um, so there's lots of programs across the country and even internationally that do this. This actually became very um, I guess uh, standard of care in the Netherlands, uh, as the first place that did this routinely. Um, so all over the world there's places that do this and so if a patient's really interested in this, they can go for a procedure at a different hospital if they're stable enough. So we have patients come in just for this procedure and then they'll go back for chemotherapy. So for those of you in the room who may not have gynecology, I don't know if you all do, who does it at your hospital? I don't know if you all have gynecologists or not. Um, does everyone here have gynecology? Okay, so I guess answer in the thread, if you don't have uh a gynecologist, who does your ovarian cryo preservation? Um, what about boys? What are we supposed to be doing? Do you, do, do that at all? Yeah, I actually know I, I don't do it, but I know about it. Um, so again, for boys it's also difficult because um, I didn't put on here egg freezing um or you know, sperm banking would be the equivalent because until kids reach puberty, you can't get mature gametes from the body. Um so sperm banking is really only an option if they have been are post pubertal. Typically tanner three and above is going to give us a better option for just banking sperm. If they're prepubertal and they're going to get high dose treatment, there are some places, um, University of Pittsburgh, um has has the protocol available that you can do testicular tissue cryo preservation. Okay. Yeah. That's what I was. And essentially, no one really does a whole oriectomy. So it's just a wedge piece. Yeah, that's what we do here. Wow. So we have the protocol here and we do it and then we ship the tissue to Pittsburgh. So any place can actually open this protocol, um and then to, you know, ship the tissue. Okay. Hey Todd, could I ask a question? So, I missed uh about the uh transplantation. At at what age is that done? So we typically just do it for pregnancy because the graph is not equivalent to a full ovary. So it only is going to last somewhere between two and five years is what the studies show. So for hormone replacement, we just use medication um for pubertal induction as well as, you know, hormones until they're ready to have pregnancy and then we put the tissue back in specifically to get. So it stays cryo preserved for whatever is 20 years or however long. However long. Yeah. Just out of curiosity, is that cryo preserved here at the University of Cincinnati or is there is that a private banking service? So we used to do the so we actually ship it offsite. So pretty much every place now uses long-term storage facilities because they have the um extra, I guess cautionary, you know, because you've heard about some of the instances of embryos or things being thought out in Cleveland as well as in um California and so I think people like having that extra security. So most of the long-term storage facility has three or four mechanisms for detecting tank dysfunction so that that doesn't happen. So ours goes to Minnesota, our tissue. But we process it in our pathology lab here. Just so just explain what happened. So there was a hospital that lost their power supply or something. Yeah. And all of the embryos that were in storage unfortunately. I think in a couple of tanks. So it wasn't all of them, but just one tank. Okay. So that's what that's why we need to maybe take some precautions. Yep. So who pays for it? And since these are young children who will move up and grow, move away, how will they be tracked or how will they know where their tissue is stored? So our team just um, so who pays for it? We'll start with that one. So the patient does pay for it. Um, typically for us, we try to team this with a different procedure. Most of our oncology patients are going to get bone marrow biopsy, they're going to get central line port. So if we place that together, then the hospital fee and the anesthesia fee often can be covered by insurance because they're going to the OR for something else. The tissue storage fee? Oh, the tissue storage fee. That is the patient. Um, so it is um income dependent. So with anyone with an oncology diagnosis, if they make under certain income, it's $75 a year. Um, and then if they make more than that, then it's $275 a year. Any other comments or questions? Okay, so